Human immunodeficiency virus (HIV) is no longer a terminal disease thanks to recent advances. However, it is still incurable. In a paper recently reported in Advanced Materials 10.1002/adma.201802233, a team led by Liangfang Zhang and Stephen Spector has come up with a creative solution to combat HIV: using nanoparticles as decoys for cells targeted by the virus.

HIV normally infects T cells and macrophages, part of the body’s immune cells that attack invaders. This kills the cells and lowers the body’s defences to attack by other pathogens. After infection, the virus persists inside host T cells, lying dormant. In Zhang and Spector’s treatment, nanoparticles are introduced that look like the host’s T cells. This tricks the HIV virus into binding to the nanoparticles rather than the real cells, preventing the infection.

With existing treatments, the virus reactivates and starts replicating again if medication is stopped. Used in conjunction with these treatments, decoy particles provide an additional mechanism to combat viral relapse, as well as the low levels of virus in the bloodstream that exist even on antiviral drugs. The particles could also be used as a preventative measure against HIV, to neutralize the virus before the infection takes hold.

Decoy nanoparticles: How to trick a virus

These nanoparticles are made of poly(lactic-co-glycolic acid) (PLGA). Zhang and Spector’s team turned them into T cell mimics by removing T cell membranes from live cells and coating them onto the nanoparticles. This gives the particle a “living skin” that makes it look just like a T cell. The scientists found that these decoy particles would successfully bind to HIV viral proteins while particles coated with red blood cell membranes or a neutral polymer would not bind to the virus. Thus, the membrane on the particle surface is enough to confuse the HIV into binding to it.

Zhang and Spector’s team also showed that the HIV virus was less infective after being incubated with their decoy particles. Furthermore, the team found that the decoy particles protected macrophages against HIV infection as well. These cells are known to act as reservoirs of HIV in the body. If they are protected from infection early on, it could keep the virus from entrenching itself inside the patient, making it easier to remove, leading to a permanent cure.

Potential treatment and innovation

As a new treatment, decoy nanoparticles are unique in that they do not depend on targeting viral proteins that quickly mutate. They work by tricking the virus into binding to a dummy target, effectively neutralizing it. Thus, the virus cannot as easily escape a decoy as it can other medications, due to the necessity of target binding for productive infection.

The team’s strategy of using the natural membranes of host cells on synthetic particles to make decoys is much more cost effective and less challenging when compared with other strategies. Although coating particles with a membrane is an established technique, The researchers envisage that this method should provide an example for treatments that can neutralize other viruses as well.

December 3, 2018

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